@article{668f2ae2ceee43cfa4915cc1f8d3a46b,
title = "MCP-1/CCR-2 axis in adipocytes and cancer cell respectively facilitates ovarian cancer peritoneal metastasis",
abstract = "Ovarian cancer selective metastasizes to the omentum contributing to the poor prognosis associated with ovarian cancer. However, the mechanism underlining this propensity and therapeutic approaches to counter this process has not been fully elucidated. Here, we show that MCP-1 produced by omental adipocytes binding to its cognate receptor CCR-2 on ovarian cancer cells facilitates migration and omental metastasis by activating the PI3K/AKT/mTOR pathway and its downstream effectors HIF-1α and VEGF-A in cell lines, xenografts, and transgenic murine models. MCP-1 antibody significantly decreased tumor burden and increased survival of mice in vivo. Interestingly, metformin decreased omental metastasis at least partially by inhibiting MCP-1 secretion from adipocytes independent of direct effects on cancer cells. Together this suggests a novel target of MCP-1/CCR-2 axis that could benefit ovarian cancer patients.",
author = "Chaoyang Sun and Xi Li and Ensong Guo and Na Li and Bo Zhou and Hao Lu and Jia Huang and Meng Xia and Wanying Shan and Beibei Wang and Kezhen Li and Danhui Weng and Xiaoyan Xu and Qinglei Gao and Shixuan Wang and Junbo Hu and Yiling Lu and Mills, {Gordon B.} and Gang Chen",
note = "Funding Information: Funding This study was supported by the National Key R&D Program of China (2016YFC1303100), the National Basic Research Program of China (973 Program, 2015CB553903), Nature and Science Foundation of China (81272859, 81572569, 81402163, 81402164, 81501530, 81671394, and 81370469), the International S&T Cooperation Program of China (No. 2013DFA31400). GBM has support from NIH P50CA217685, Ovarian Cancer Research Foundation, and a kind gift from the Adelson Medical Research Fund. Funding Information: Research Foundation, AstraZeneca, Breast Cancer Research Foundation, Immunomet, Ionis, Komen Research Foundation, Nanostring, Ovarian Cancer Research Foundation, Pfizer, Prospect Creek Foundation, and Takeda/Millennium Pharmaceuticals. The authors declare that they have no conflict of interest. Funding Information: SKOV3 cells were culture with or without MCP-1 (10 or 20 μg/L) for 24. Protein lysates were analyzed by RPPA in MDACC CCSG (The Cancer Center Support Grant) supported RPPA Core. Antibodies and approaches are described at the RPPA website (https://www.mdanderson.org/ research/research-resources/core-facilities/functional-proteomics-rppa-core.html). Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2020",
month = feb,
day = "20",
doi = "10.1038/s41388-019-1090-1",
language = "English (US)",
volume = "39",
pages = "1681--1695",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "8",
}